Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32250 | 96973;96974;96975 | chr2:178543225;178543224;178543223 | chr2:179407952;179407951;179407950 |
| N2AB | 30609 | 92050;92051;92052 | chr2:178543225;178543224;178543223 | chr2:179407952;179407951;179407950 |
| N2A | 29682 | 89269;89270;89271 | chr2:178543225;178543224;178543223 | chr2:179407952;179407951;179407950 |
| N2B | 23185 | 69778;69779;69780 | chr2:178543225;178543224;178543223 | chr2:179407952;179407951;179407950 |
| Novex-1 | 23310 | 70153;70154;70155 | chr2:178543225;178543224;178543223 | chr2:179407952;179407951;179407950 |
| Novex-2 | 23377 | 70354;70355;70356 | chr2:178543225;178543224;178543223 | chr2:179407952;179407951;179407950 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs866570041  |
None | 0.27 | N | 0.289 | 0.14 | 0.480801007081 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/I | rs866570041 |
None | 0.27 | N | 0.289 | 0.14 | 0.480801007081 | gnomAD-4.0.0 | 1.31515E-05 | None | None | None | None | I | None | 2.41488E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47037E-05 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4713 | ambiguous | 0.441 | ambiguous | -1.183 | Destabilizing | 0.329 | N | 0.329 | neutral | None | None | None | None | I |
| M/C | 0.7008 | likely_pathogenic | 0.7046 | pathogenic | -0.79 | Destabilizing | 0.981 | D | 0.35 | neutral | None | None | None | None | I |
| M/D | 0.8079 | likely_pathogenic | 0.7971 | pathogenic | -0.061 | Destabilizing | 0.543 | D | 0.366 | neutral | None | None | None | None | I |
| M/E | 0.4763 | ambiguous | 0.4646 | ambiguous | -0.066 | Destabilizing | 0.704 | D | 0.376 | neutral | None | None | None | None | I |
| M/F | 0.3786 | ambiguous | 0.3689 | ambiguous | -0.393 | Destabilizing | 0.893 | D | 0.325 | neutral | None | None | None | None | I |
| M/G | 0.5655 | likely_pathogenic | 0.5471 | ambiguous | -1.44 | Destabilizing | 0.495 | N | 0.382 | neutral | None | None | None | None | I |
| M/H | 0.4753 | ambiguous | 0.4828 | ambiguous | -0.471 | Destabilizing | 0.944 | D | 0.324 | neutral | None | None | None | None | I |
| M/I | 0.4012 | ambiguous | 0.3657 | ambiguous | -0.558 | Destabilizing | 0.27 | N | 0.289 | neutral | N | 0.432534685 | None | None | I |
| M/K | 0.2446 | likely_benign | 0.2464 | benign | -0.169 | Destabilizing | 0.642 | D | 0.347 | neutral | N | 0.431321177 | None | None | I |
| M/L | 0.1343 | likely_benign | 0.129 | benign | -0.558 | Destabilizing | 0.002 | N | 0.114 | neutral | N | 0.438401865 | None | None | I |
| M/N | 0.4169 | ambiguous | 0.3845 | ambiguous | -0.01 | Destabilizing | 0.031 | N | 0.237 | neutral | None | None | None | None | I |
| M/P | 0.9565 | likely_pathogenic | 0.9492 | pathogenic | -0.738 | Destabilizing | 0.944 | D | 0.361 | neutral | None | None | None | None | I |
| M/Q | 0.1956 | likely_benign | 0.2058 | benign | -0.125 | Destabilizing | 0.828 | D | 0.313 | neutral | None | None | None | None | I |
| M/R | 0.2541 | likely_benign | 0.2576 | benign | 0.363 | Stabilizing | 0.784 | D | 0.38 | neutral | N | 0.442500963 | None | None | I |
| M/S | 0.397 | ambiguous | 0.3815 | ambiguous | -0.564 | Destabilizing | 0.037 | N | 0.15 | neutral | None | None | None | None | I |
| M/T | 0.2857 | likely_benign | 0.2635 | benign | -0.463 | Destabilizing | 0.27 | N | 0.351 | neutral | N | 0.404289291 | None | None | I |
| M/V | 0.1319 | likely_benign | 0.1249 | benign | -0.738 | Destabilizing | 0.27 | N | 0.308 | neutral | N | 0.416026438 | None | None | I |
| M/W | 0.6124 | likely_pathogenic | 0.6342 | pathogenic | -0.331 | Destabilizing | 0.995 | D | 0.359 | neutral | None | None | None | None | I |
| M/Y | 0.5537 | ambiguous | 0.5573 | ambiguous | -0.308 | Destabilizing | 0.944 | D | 0.356 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.